Muscle Fiber Cross-sectional Area Research Articles

MeRIP sequencing reveals the regulation of N6-methyladenosine in muscle development between hypertrophic and leaner broilers

Meat production performance is the most important economic trait in broilers, and skeletal muscle, as the largest organ in animals, is directly related to meat production during embryonic and postnatal growth and development. N6-Methyladenosine (m6A) is a chemical modification occurs on RNA adenosine that has been reported to participate in a variety of biological processes in all species. However, there are still few reports on the regulatory role of muscle growth and development in poultry after birth. This study aims to reveal the distribution of m6A modification sites in chicken pectoralis major muscle after birth and find out the regulatory relationship between m6A and muscle development. As representatives of leaner (Xinghua chicken [XH]) and hypertrophic (White Recessive Rock chicken [WRR]) broilers, there are significant differences in body weight, muscle fiber diameter, and muscle fiber cross-sectional area between XH and WRR chickens. RNA sequencing detected a total of 397 differentially expressed genes (DEG) in the pectoralis major muscle of XH and WRR chicken, and these DEGs were mainly enriched in catalytic activity and metabolic pathways. MeRIP sequencing results showed that among all 6,476 differentially modified m6A peaks, about 90% peaks (5,823) were differentially down regulated in XH chickens. The joint analysis of the mRNA and MeRIP sequencing data found 145 DEGs with differential m6A peak, ALKBH5 as a m6A demethylase, was also included. The highly expression of ALKBH5 in the muscle tissue of poultry and differential expression between XH and WRR chickens suggest that ALKBH5 may play a crucial role in regulating muscle development. Our results revealed that there were significant differences in growth rate, body weight, muscle fiber diameter, and fiber cross-section area between WRR and XH chicken, as well as significant differences in m6A methylation level and muscle metabolism level.

Postnatal survival of phrenic motor neurons is promoted by BDNF/TrkB.FL signaling.

The number of motor neurons (MNs) declines precipitously during the final trimester before birth. Thereafter, the number of MNs remains relatively stable, with their connections to skeletal muscle dependent on neurotrophins, including brain-derived neurotrophic factor (BDNF) signaling through its high-affinity full-length tropomyosin-related kinase receptor subtype B (TrkB.FL) receptor. As a genetic knockout of BDNF leads to extensive MN loss and postnatal death within 1-2 days after birth, we tested the hypothesis that postnatal inhibition of BDNF/TrkB.FL signaling is important for postnatal phrenic MN (PhMN) survival. In the present study, we used a 1NMPP1-sensitive TrkBF616A mutant mouse to evaluate the effects of inhibition of TrkB kinase activity on phrenic MN (PhMN) numbers and diaphragm muscle (DIAm) fiber cross-sectional area (CSA). Pups were exposed to 1NMPP1 or vehicle (DMSO) from birth to 21 days old (weaning) via the mother's ingestion in the drinking water. Following weaning, the right phrenic nerve was exposed in the neck and the proximal end dipped in a rhodamine solution to retrogradely label PhMNs. After 24 h, the cervical spinal cord and DIAm were excised. Labeled PhMNs were imaged using confocal microscopy, whereas DIAm strips were frozen at ∼1.5× resting length, cryosectioned, and stained with hematoxylin and eosin to assess CSA. We observed an ∼34% reduction in PhMN numbers and increased primary dendrite numbers in 1NMPP1-treated TrkBF616A mice. The distribution of PhMN size (somal surface area) DIAm fiber cross-sectional areas did not differ. We conclude that survival of PhMNs during early postnatal development is sensitive to BDNF/TrkB.FL signaling.NEW & NOTEWORTHY During early postnatal development, BDNF/TrkB signaling promotes PhMN survival. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact PhMN size. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact the number or CSA of DIAm fibers.

Belt electrode tetanus muscle stimulation reduces denervation-induced atrophy of rat multiple skeletal muscle groups

Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon.

Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

Sex Differences in Quadriceps Atrophy After Anterior Cruciate Ligament Tear.

Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex. Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients. Cross-sectional study. Level 4. A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest. The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups. Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients. These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.

Resistance exercise preconditioning prevents disuse muscle atrophy by inhibiting apoptosis and protein degradation via SESN2 in C57BL/6J mice

AimTo compare the effects of different exercise preconditioning in the context of skeletal muscle atrophy and to investigate the potential involvement of Sestrin2 (SESN2), a stress-inducible protein that can be regulated by exercise, in exercise preconditioning on preventing disuse muscle atrophy. MethodsEight-week-old male C57BL/6J mice were randomly assigned to sedentary groups (SD), aerobic exercise groups (AE), resistance exercise groups (RE), and combined exercise groups (CE) with or without 7 days of immobilization. The duration of the exercise intervention was 10 weeks. The effects of different exercise preconditioning to prevent muscle atrophy were analyzed by evaluating skeletal muscle function and mass. Additionally, to investigate the potential underlying mechanism of exercise-induced protection of skeletal muscle, wild-type and SESN2‐−/‐− mice were randomly divided into sedentary group and resistance exercise preconditioning group. C2C12 cells were treated with SESN2 adenoviruses and MK2206 (an AKT inhibitor) for 48 h to elucidate the underlined mechanism. ResultsRE was more effective in preserving skeletal muscle function, muscle mass and maintaining skeletal muscle protein homeostasis than AE and CE under immobilized condition. Importantly, exercise performance, muscle mass to body weight ratio, and the cross-sectional area of muscle fibers were significantly lower in SESN2−/− mice than wild-type mice after resistance exercise preconditioning. Mechanistically, the absence of SESN2 led to activation of the ubiquitin-proteasome system and induction of apoptosis. In vitro experiments showed that MK2206 treatment mitigated the regulatory effects of overexpression-SESN2 on protein hydrolysis and apoptosis. ConclusionRE was more effective than AE or CE in preventing disuse muscle atrophy. SESN2 mediated the protective effects of resistance exercise preconditioning on skeletal muscle atrophy.

Skeletal muscle adaptations to high-intensity, low-volume concurrent resistance and interval training in recreationally active men and women.

This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12-week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high-intensity, low-volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre- and post-training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross-sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC-1α (29.7%, p < 0.001) and citrate synthase (11.0%; p < 0.014) content, but had no effect on COX IV content or muscle capillarization. In both sexes, training increased maximal strength and LBM but not aerobic capacity. The concurrent training program was effective at increasing strength and LBM but not at improving aerobic capacity or skeletal muscle adaptations underpinning aerobic performance.

Dietary pyrroloquinoline quinone hinders aging progression in male mice and D-galactose-induced cells.

Background: Understanding and promoting healthy aging has become a necessity in the modern world, where life expectancy is rising. The prospective benefits of the antioxidant pyrroloquinoline quinone (PQQ) in healthy aging are promising. However, its role in aging remains unclear. Thus, this study aimed to investigate the effect of PQQ on preventing the progression of aging and to explore its underlying molecular mechanisms. Methods: Naturally aged C57BL/6J male mice were fed a normal diet with or without PQQ (20mg/kg/day) for 10 weeks. Body composition was measured by bioimpedance at weeks 0 and 8. The integument conditions were evaluated at weeks 0, 4, and 8. Muscle strength and function were examined at week 8. At the ninth week, computed tomography images of the mice were captured, and blood and tissue samples were collected. The levels of inflammatory cytokines in the gastrocnemius muscle were measured, and the muscle fiber cross-sectional area in the soleus muscle was examined. Additionally, a D-galactose (D-gal)-induced cell aging model was used to study the effects of PQQ intervention on cell proliferation, senescence, differentiation, ROS levels, and mitochondrial function in myoblasts (C2C12). Cell proliferation and monolayer permeability of D-gal-induced intestinal epithelial cells (IEC6) were also examined. Results: Aged mice suffered from malnutrition; however, PQQ supplementation ameliorated this effect, possibly by improving metabolic dysfunction and small intestinal performance. PQQ prevented rapid loss of body fat and body fluid accumulation, attenuated muscle atrophy and weakening, reduced chronic inflammation in skeletal muscles, and improved skin and coating conditions in aged mice. Furthermore, PQQ intervention in D-gal-treated C2C12 cells improved mitochondrial function, reduced cellular reactive oxygen species (ROS) levels and senescence, and enhanced cell differentiation, consequently preventing age-related muscle atrophy. In addition, PQQ increased cell proliferation in D-gal-treated IEC6 cells and consequently improved intestinal barrier function. Conclusion: PQQ could hinder the aging process and particularly attenuate muscle atrophy, and muscle weakness by improving mitochondrial function, leading to reduced age-related oxidative stress and inflammation in muscles. PQQ may also ameliorate malnutrition caused by intestinal barrier dysfunction by enhancing IEC proliferation. This study provides evidence for the role of PQQ in aging and suggests that PQQ may be a potential nutritional supplementation that can be included in healthy aging strategies.

Effects of low-load resistance training with blood flow restriction on muscle fiber myofibrillar and extracellular area.

Blood flow restriction applied during low-load resistance training (LL-BFR) induces a similar increase in the cross-sectional area of muscle fibers (fCSA) compared to traditional high-load resistance training (HL-RT). However, it is unclear whether LL-BFR leads to differential changes in myofibrillar spacing in muscle fibers and/or extracellular area compared to HL-RT. Therefore, this study aimed to investigate whether the hypertrophy of type I and II fibers induced by LL-BFR or HL-RT is accompanied by differential changes in myofibrillar and non-myofibrillar areas. In addition, we examined if extracellular spacing was differentially affected between these two training protocols. Twenty recreationally active participants were assigned to LL-BFR or HL-RT groups and underwent a 6-week training program. Muscle biopsies were taken before and after the training period. The fCSA of type I and II fibers, the area occupied by myofibrillar and non-myofibrillar components, and extracellular spacing were analyzed using immunohistochemistry techniques. Despite the significant increase in type II and mean (type I + II) fCSA (p < 0.05), there were no significant changes in the proportionality of the myofibrillar and non-myofibrillar areas [∼86% and ∼14%, respectively (p > 0.05)], indicating that initial adaptations to LL-BFR are primarily characterized by conventional hypertrophy rather than disproportionate non-myofibrillar expansion. Additionally, extracellular spacing was not significantly altered between protocols. In summary, our study reveals that LL-BFR, like HL-RT, induces skeletal muscle hypertrophy with proportional changes in the areas occupied by myofibrillar, non-myofibrillar, and extracellular components.

Muscle Fiber Cross-Sectional Area Is Associated With Quadriceps Strength and Rate of Torque Development After ACL Injury.

Graham, MC, Thompson, KL, Hawk, GS, Fry, CS, and Noehren, B. Muscle fiber cross-sectional area is associated with quadriceps strength and rate of torque development after ACL injury. J Strength Cond Res 38(6): e273-e279, 2024-The purpose of this study was to investigate the relationship between muscle fiber type-specific properties of the vastus lateralis and quadriceps muscle performance in individuals after an anterior cruciate ligament (ACL) tear. 26 subjects (22.0 ± 5.4 years) were included in this cross-sectional study, and all data were collected before ACL reconstruction. Quadriceps peak torque (QPT) and early (0-100 ms) and late (100-200 ms) rate of torque development (RTD) were obtained from maximal voluntary isometric quadriceps strength testing. Muscle fiber cross-sectional area (fCSA) and percent fiber type distribution (FT%) were evaluated through immunohistochemical analysis of a muscle biopsy. Between-limb differences in fiber characteristics were assessed using paired t-tests (with α-level 0.05). Relationships between fiber-specific properties and quadriceps muscle performance were determined using separate multiple linear regression analyses for ACL-injured and noninjured limbs. There were significant differences in fCSA between ACL-injured and noninjured limbs across all fiber types, but no differences in FT%. Type 1 fCSA, type 2a fCSA, and their interaction effect were the explanatory variables with the strongest relationship to all performance outcomes for the ACL-injured limb. The explanatory variables in the ACL-injured limb had a significant relationship to QPT and late RTD, but not early RTD. These findings suggest that QPT and late RTD are more heavily influenced by fCSA than FT% in ACL-injured limbs. This work serves as a foundation for the development of more specific rehabilitation strategies aimed at improving quadriceps muscle function before ACL reconstruction or for individuals electing nonsurgical management.

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L-1 vs. 4.26 ± 0.6 mmol L-1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min-1 vs. 34.75 ± 2.66 m min-1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg-1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p.

Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and β-catenin. F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimickingthe remarkable myogenic differentiation potential of hFCPCs.

FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.

Fibroblast growth factor-21 (FGF21) is an intercellular signaling molecule secreted by metabolic organs, including skeletal muscle, in response to intracellular stress. FGF21 crosses the blood-brain barrier and acts via the nervous system to coordinate aspects of the adaptive starvation response, including increased lipolysis, gluconeogenesis, fatty acid oxidation, and activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Given its beneficial effects for hepatic lipid metabolism, pharmaceutical FGF21 analogues are used in clinical trials treatment of fatty liver disease. We predicted pharmacologic treatment with FGF21 increases HPA axis activity and skeletal muscle glucocorticoid signaling and induces skeletal muscle atrophy in mice. Here we found a short course of systemic FGF21 treatment decreased muscle protein synthesis and reduced tibialis anterior weight; this was driven primarily by its effect in female mice. Similarly, intracerebroventricular FGF21 reduced tibialis anterior muscle fiber cross-sectional area; this was more apparent among female mice than male littermates. In agreement with the reduced muscle mass, the topmost enriched metabolic pathways in plasma collected from FGF21-treated females were related to amino acid metabolism, and the relative abundance of plasma proteinogenic amino acids was increased up to 3-fold. FGF21 treatment increased hypothalamic Crh mRNA, plasma corticosterone, and adrenal weight, and increased expression of glucocorticoid receptor target genes known to reduce muscle protein synthesis and/or promote degradation. Given the proposed use of FGF21 analogues for the treatment of metabolic disease, the study is both physiologically relevant and may have important clinical implications.

Exercise-induced modulation of myokine irisin on muscle-bone unit in the rat model of post-traumatic osteoarthritis

Background and aimPost-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear.MethodsEighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia.ResultsEight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action.ConclusionTreadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit.

Therapeutic Effect of AAV8-Mediated miR-23a in Immobilization-Induced Muscle Atrophy in Mice

bjective: To investigate the therapeutic effect of miR-23a in immobilization-induced muscle atrophy in mice. Methods: (Experiment 1) Twelve C57BL6 wild-type mice were randomly divided into two groups: Sham group (sham surgery) and Immobilization (hind limb immobilization surgery). Fluorescence quantitative PCR was performed to detect the expression changes of miR-23a, MuRF-1, and Atrogin-1 7 days post-surgery. (Experiment 2) Twelve C57BL6 wild-type mice were randomly divided into 4 groups according to surgery type (sham surgery and hind limb immobilization surgery) and injection type (AAV8 or AAV8-OEmiR-23a), fluorescence quantitative PCR to detect changes in MuRF-1 and Atrogin-1 expression in mouse gastrocnemius muscle. (Experiment 3) NFATc3 expression changes were detected by fluorescence quantitative PCR 48 hours post-transfection. (Experiment 4) Twelve C57BL6 wild-type mice underwent hind limb immobilization surgery, divided into 4 groups : Immobilization+AAV8-control, Immobilization+AAV8-OEmiR23a, Immobilization+AAV8-shNFATc3, and Immobilization+AAV8-OEmiR-23a+AAV8-shNFATc3. quantitative PCR to detect changes in MuRF-1 and Atrogin-1 expression in mouse gastrocnemius muscle. Results: Fluorescence quantitative PCR results showed that miR-23a was downregulated in immobilization-induced muscle atrophy, while MuRF-1 and Atrogin-1 expression was upregulated. WGA staining results showed that intramuscular injection of AAV8-OEmiR-23a could significantly alleviate the decrease in muscle fiber cross-sectional area and the increase in expression of muscle atrophy marker genes MuRF-1 and Atrogin-1 caused by hind limb immobilization, Fluorescence quantitative PCR revealed that when miR-23a expression was inhibited, NFATc3 expression was downregulated; when miR-23a was overexpressed, NFATc3 expression was upregulated, Fluorescence quantitative PCR results showed that intramuscular injection of AAV8-OEmiR-23a and AAV8-shNFATc3 could not alleviate the increase in expression of muscle atrophy marker genes MuRF-1 and Atrogin-1 caused by hind limb immobilization. Conclusion: miR-23a can treat hind limb immobilization-induced muscle atrophy in mice.

Comparison of Chemical Composition, Quality, and Muscle Fiber Characteristics between Cull Sows and Commercial Pigs: The Relationship between Pork Quality Based on Muscle Fiber Characteristics.

This study aims to compare the chemical composition, quality, and muscle fiber characteristics of cull sows and commercial pigs, investigating the effect of changes in muscle fiber characteristics on pork quality. The proximate composition, color, pH, water-holding capacity (drip loss and cooking loss), protein solubility, total collagen content, and muscle fiber characteristics of cull sows (n=20) and commercial pigs (n=20) pork were compared. No significant differences were found between cull sows and commercial pigs in terms of proximate composition, drip loss, protein solubility, or total collagen content of their meat (p<0.05). However, cull sow pork exhibited a red color and a higher pH (p<0.05). This appears to be the result of changes in muscle fiber number and area composition (p<0.05). Cull sow meat also displayed better water-holding capacity as evident in a smaller cooking loss (p<0.05), which may be related to an increase in muscle fiber cross-sectional area (p<0.05). In conclusion, muscle fiber composition influences the pork quality; cull sow pork retains more moisture when cooked, resulting in minimal physical loss during processing and can offer more processing suitability.

Becoming a World Champion Powerlifter at 71Years of Age: It Is Never Too Late to Start Exercising.

This case study assessed body composition, muscle strength, cardiorespiratory fitness, and metabolic health of the present female world champion powerlifter in the 70+ age category who started resistance exercise training at 63years of age with no prior experience with structured exercise training. Measures of body composition (magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry scanning, leg volume); strength (one-repetition maximum leg press and extension, maximum voluntary contraction, and handgrip strength); physical function (short physical performance battery); cardiorespiratory fitness (peak oxygen consumption); and metabolic health (oral glucose tolerance test) were assessed. In addition, a muscle biopsy was collected to assess muscle fiber type distribution and cross-sectional area (CSA). Where possible, data were compared with previously (un)published sex- and age-matched data using z scores. Skeletal muscle mass index was calculated by dividing limb muscle mass by height squared. Data from the control groups are expressed as mean ± 95% confidence interval. Our participant (age: 71years; body mass: 64.5kg; body mass index: 27.6kg/m2) reported a good bone mineral density of 1.09g/cm2 (T score between -1 and +1) and very low values of abdominal and organ body fat (i.e.,between 20% and 70% lower compared with a reference group of postmenopausal women). In addition, she showed a 33% greater skeletal muscle mass index when compared with healthy, older female control subjects (7.9 vs. 5.9 [5.7-6.2] kg/m2; n = 61) as well as 37% greater muscle quadriceps CSA (63.8 vs. 46.6 [44.5-48.7] cm2; n = 48) and 46% greater Type II muscle fiber CSA (4,536 vs. 3,097 [2,707-3,488] μm2; n = 19). Absolute leg press muscle strength was 36% greater (190 vs. 140 [132-147] kg; n = 30) and handgrip strength was 33% greater (33 vs. 25 [23-26] kg; n = 48) when compared with healthy, age-matched controls. In conclusion, even for resistance exercise naïve individuals, starting exercise at an advanced age can lead to improvements in body composition and muscle strength allowing older adults to reduce the risk for developing metabolic syndrome, live independently, and even compete at a world class level.

Development of myofibers and muscle transcriptomic analysis in growing Yili geese

In poultries, muscle growth is a quantitative trait controlled by multiple genes. The regulatory mechanisms governing muscle tissue growth and development in poultry, particularly during the early stages of growth, are intricate. Through the examination of leg muscle transcripts from Yili geese during various stages of development, this study offers valuable insights into the molecular mechanisms underlying the growth and development of Yili geese. This study aimed to perform a comparative analysis of the histological characteristics of leg muscles and the mRNA expression profiles of leg muscles in Yili geese at different ages (2, 4, 6, 8, and 10 wk). The objective was to identify differentially expressed genes related to muscle development in Yili geese and utilize bioinformatics to predict the potential biological functions of these genes. Through histological studies on leg muscle tissues, it was discerned that male geese at 4 wk exhibit a significantly reduced muscle fiber density in comparison to females (P < 0.01). In contrast, by the time they reach 6, 8, and 10 wk, their muscle fiber diameter and cross-sectional dimensions significantly outpace the females (P < 0.01). With the advancement in age, muscle fiber density tends to decrease. It is worth noting that 4- and 6-wk-old male geese have a substantially elevated muscle fiber density when matched against females (P < 0.01). Conversely, at the age of 10 wk, their muscle fiber density is notably inferior to the females (P < 0.01). Furthermore, male geese exhibit the most rapid increase in muscle fiber diameter and cross-sectional area between 4 and 6 wk of age. The density of muscle fibers in these geese significantly decreases from 4 to 8 wk. In contrast, female geese show the most pronounced growth in muscle fiber diameter and cross-sectional area between 2 and 6 wk, with a swift decline in density following the 6-wk mark, accompanied by a gradual reduction in the rate of muscle fiber growth. A comprehensive analysis of the leg muscle mRNA expression profiles from 12 Yili geese generated a cumulative total of 502,065,268 valid sequence reads, corresponding to a data volume of 75.30 Gb. In a comparative analysis between 4-wk-old and 2-wk-old groups (T4 vs. T2), 8-wk-old and 2-wk-old groups (T8 vs. T2), and 8-wk-old and 4-wk-old groups (T8 vs. T4), we identified 1,700, 1,583, and 221 differentially expressed genes (DEGs), respectively. Differentially expressed genes were significantly enriched in Gene Ontology (GO) terms such as organelle organization, cytoskeletal protein binding, cation transport, myosin complex, and actin cytoskeleton. Among the significantly enriched signaling pathways, 5 pathways were found to be significantly related to growth and development: adhesion patch, extracellular matrix receptor interaction, tight junction, TGF-β signaling pathway, and MAPK signaling pathway, with a total of 38 differentially differentiated genes contained in these 5 pathways, and it was hypothesized that the above pathways as well as the DEGs in the pathways played an important role in the regulation of early growth and development of the Yili goose. This investigation serves as a foundational reference for elucidating the molecular regulatory mechanisms involved in the development of goose muscle. Furthermore, it contributes to the expansion of the theoretical framework concerning the genetic regulation of muscle growth in geese.

Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.

BACKGROUNDAlthough 25-hydroxyvitamin D [25(OH)D] concentrations of 30 ng/mL or higher are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets after ACLR.METHODSTwenty-one young, healthy, physically active participants with recent ACL tears were enrolled (17.8 ± 3.2 years, BMI 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, dual energy x-ray bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months after ACLR. The biopsies facilitated CSA, Western blotting, RNA-seq, and VDR ChIP-seq analyses.RESULTSACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle 1 week after ACLR. Participants with less than 30 ng/mL 25(OH)D levels (n = 13) displayed more significant quadriceps fiber CSA loss 1 week and 4 months after ACLR than those with 30 ng/mL or higher (n = 8; P < 0.01 for post hoc comparisons; P = 0.041 for time × vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density losses between groups was observed.CONCLUSIONCorrecting vitamin D status prior to ACLR may aid in preserving skeletal muscle during recovery.FUNDINGNIH grants R01AR072061, R01AR071398-04S1, and K99AR081367.

Regular exercise attenuates alcoholic myopathy in zebrafish by modulating mitochondrial homeostasis.

Alcoholic myopathy is caused by chronic consumption of alcohol (ethanol) and is characterized by weakness and atrophy of skeletal muscle. Regular exercise is one of the important ways to prevent or alleviate skeletal muscle myopathy. However, the beneficial effects and the exact mechanisms underlying regular exercise on alcohol myopathy remain unclear. In this study, a model of alcoholic myopathy was established using zebrafish soaked in 0.5% ethanol. Additionally, these zebrafish were intervened to swim for 8 weeks at an exercise intensity of 30% of the absolute critical swimming speed (Ucrit), aiming to explore the beneficial effects and underlying mechanisms of regular exercise on alcoholic myopathy. This study found that regular exercise inhibited protein degradation, improved locomotion ability, and increased muscle fiber cross-sectional area (CSA) in ethanol-treated zebrafish. In addition, regular exercise increases the functional activity of mitochondrial respiratory chain (MRC) complexes and upregulates the expression levels of MRC complexes. Regular exercise can also improve oxidative stress and mitochondrial dynamics in zebrafish skeletal muscle induced by ethanol. Additionally, regular exercise can activate mitochondrial biogenesis and inhibit mitochondrial unfolded protein response (UPRmt). Together, our results suggest regular exercise is an effective intervention strategy to improve mitochondrial homeostasis to attenuate alcoholic myopathy.